Immunization with plasmid DNA has been shown to induce protective immunity in a variety of experimental models of infection. The ability of DNA vaccination to elicit both MHC class I and class II restricted T cell responses has been shown to be responsible for mediating these protective immune responses. Thus, DNA vaccination can provide a useful and an effective way in providing effective immunity to particular pathogens depending on the type of immunity required for protection. We have identified a number of mouse experimental models in which to develop an understanding for the utility of DNA vaccination. For infectious diseases, this includes mouse models for Leishmania major (L. major), and Mycobacterium tuberculosis. In addition this work is being applied to primate studies using DNA vaccines for cutaneous leishmania infection as well as HIV. The work involves identifying cloned antigens for the specific infectious agent and cloning it into an appropriate euykaryotic expression vector. In addition, we have obtained DNA for a number of cytokines and costimulatory molecules to be used as adjuvants to the specific antigens. Following purification of the DNA, mice are then injected and boosted several weeks later. At various times following the vaccination, mice are infected with a particular pathogen. Parameters that are followed include survival, quantitation of infectious burden, and immunologic studies of antibody and cytokine production. Current work using DNA vaccination has made the following observations.1) DNA vaccination induces long-term cellular immune responses sufficient to protect mice against challenge against Leishmania major.2) Plasmid DNA vaccination encoding a specific leishmanial antigen induces both CD4 and CD8+ induction of IFN-g in response following vaccination. By contrast, vaccination with leishmanial protein plus IL-12 induces only CD4+ T cell production of IFN-g.3) Induction of leishmanial specific CD4+ IFN-g producing T cells is relatively short lived following vaccination with leishmanial protein plus IL-12.4) A continuous source of IL-12 is required to sustain long term immunity against L. major infection and maintain the frequency of CD4+/IFN-g producing cells.